Towards multiscale modelling of thylakoid membranes

The project deals with the development and validation of a first set of methods for full thylakoid modeling, including all relevant components (proteins, lipids, etc.) and thermodynamic (transport) processes. The rationale is that at some point in the future, maybe as little as 10-20 years from now, genetic biomolecular engineers will be able to rationally design an optimal scaffold for (photo-)biochemical processes, the same as exists in current artificial macro- or microreactors in chemical engineering. No doubt that such a futuristic model will still be highly abstracted from the actual complex biosystem, but even with such reduction, it is clear that such an engineering approach calls for a number of simulation methods that are still at its infancy, or simply do not exist at all. The challenges that the modeler faces can be divided into two: (i) Accelerated equilibration. A specific practical requirement is that, within a reasonable time of a day or even less on a reasonable sized hardware of a few ten cores, an engineer must be able to calculate thermodynamic properties and stability of a micron-size scaffold. Currently, our group develops a new generation of physical-inspired optimizers named S-QN, that may enable such an ambitious goal in the near future. (ii) Automatic parameterization of all molecular components from atomistic to mesoscopic or automated coarse-graining. Here, the requirement is that such an engineer must be able to deal with the huge diversity of potentially thousands of chemical components without manual intervention, using a protocol with a sound theoretical basis. Additional aspects, such as the generating of the chemical diversity, or reading in templates from experimental scaffolds are equally important but not considered here. The project is supported by Culgi BV, and will be using the Culgi simulation platform. The commercial interest for Culgi BV is immediate, since these methods are in focus of industrial computational chemistry. The validation of such novel simulation and parameterization methods is of interest to a very large range of industrial soft matter systems, ranging from surfactant enhanced crude oil recovery and engineering plastics, to emulsion based drug delivery, to personal care products formulations (shampoo, hair conditioners); in all these cases one has the same issues of complex amphiphilic scaffold stability and diversity. Sub-project (i), extending S-QN, will be carried out by a post-doc at the SMC laboratory (candidate available) at the Leiden Institute of Chemistry. Sub-project (ii), validation of automated parameterization (AP), will be carried out at Culgi BV office, Leiden. In both cases, the validation method will consist of a script (either Tcl, Python, GPE, or C++) that will interface to the Culgi library. Here, the library is background and the scripts foreground. The scripts will be open source, and made freely available to the scientific community at large.

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